Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  26 TAGFSPSDGrpALEIVLGAINNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTAVTYLINQGVPVH 105
Cdd:cd09170    3 EVYFSPEGG--ARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 487691887 106 LNGRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDAPQLAETYQREFNRLWDE 167
Cdd:cd09170   81 IDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  26 TAGFSPSDGrpALEIVLGAINNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTAVTYLINQGVPVH 105
Cdd:cd09170    3 EVYFSPEGG--ARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 487691887 106 LNGRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDAPQLAETYQREFNRLWDE 167
Cdd:cd09170   81 IDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  10 AAALCVPAFATAAPVLTAGFSPSDGRPALE-IVLGAINNARQSIDVAAYSFT-SKPVATALAGANRRGVAVRVVADEKAN 87
Cdd:COG1502  176 GEALPFPEPAGDVRVQVVPSGPDSPRETIErALLAAIASARRRIYIETPYFVpDRSLLRALIAAARRGVDVRILLPAKSD 255

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  88 SDRYTAVTY-----LINQGVPVHLNGRyAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDaPQLAETYQREFN 162
Cdd:COG1502  256 HPLVHWASRsyyeeLLEAGVRIYEYEP-GFLHAKVMVVDDEWALVGSANLDPRSLRLNFEVNLVIYD-PEFAAQLRARFE 333

                 ....*....
gi 487691887 163 RLWDEGTPL 171
Cdd:COG1502  334 EDLAHSREV 342

Phospholipase D. Active site motifs; Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, aspartic acid, and/or asparagine residues which may contribute to the active site. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

                           10        20
                   ....*....|....*....|..
gi 487691887   112 IMHNKFMVIDGKNVQTGSFNYT 133
Cdd:smart00155   4 VLHTKLMIVDDEIAYIGSANLD 25

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  26 TAGFSPSDGrpALEIVLGAINNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTAVTYLINQGVPVH 105
Cdd:cd09170    3 EVYFSPEGG--ARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKSQAGGKYSALNYLANAGIPVR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 487691887 106 LNGRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDAPQLAETYQREFNRLWDE 167
Cdd:cd09170   81 IDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWAQ 142

Catalytic domain of vertebrate phospholipase D6 and similar proteins; Catalytic domain of vertebrate phospholipase D6 (PLD6, EC 3.1.4.4), a homolog of the EDTA-resistant nuclease Nuc from Salmonella typhimurium, and similar proteins. PLD6 can selectively hydrolyze the terminal phosphodiester bond of phosphatidylcholine (PC) with the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. It also catalyzes the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. PLD6 belongs to the phospholipase D (PLD) superfamily. Its monomer contains a short conserved sequence motif, H-x-K-x(4)-D (where x represents any amino acid residue), termed the HKD motif, which is essential in catalysis. PLD6 is more closely related to the nuclease Nuc than to other vertebrate phospholipases, which have two copies of the HKD motif in a single polypeptide chain. Like Nuc, PLD6 may utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from the HKD motif of one subunit to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  29 FSPSDgrPALEIVLGAINNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTAVTYLINQGVPVHLNG 108
Cdd:cd09171    3 FFPGE--TSLSKLLRYLLSARKSLDVCVFTITCDDLADAILDLHRRGVRVRIITDDDQMEDKGSDIGKLRKAGIPVRTDL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 487691887 109 RYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDaPQLAETYQREFNRLW 165
Cdd:cd09171   81 SSGHMHHKFAVIDGKILITGSFNWTRQAVTGNQENVLITND-PKLVKPFTEEFEKLW 136

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  10 AAALCVPAFATAAPVLTAGFSPSDGRPALE-IVLGAINNARQSIDVAAYSFT-SKPVATALAGANRRGVAVRVVADEKAN 87
Cdd:COG1502  176 GEALPFPEPAGDVRVQVVPSGPDSPRETIErALLAAIASARRRIYIETPYFVpDRSLLRALIAAARRGVDVRILLPAKSD 255

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  88 SDRYTAVTY-----LINQGVPVHLNGRyAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDaPQLAETYQREFN 162
Cdd:COG1502  256 HPLVHWASRsyyeeLLEAGVRIYEYEP-GFLHAKVMVVDDEWALVGSANLDPRSLRLNFEVNLVIYD-PEFAAQLRARFE 333

                 ....*....
gi 487691887 163 RLWDEGTPL 171
Cdd:COG1502  334 EDLAHSREV 342

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  41 VLGAINNARQSIDVAAYSFTSKP--------VATALAGANRRGVAVRVVADEKANSDRYT-----AVTYLINQGVPVHLN 107
Cdd:cd09131    8 LLDLINNAKRSIYIAMYMFKYYEnpgngvntLLEALIDAHKRGVDVKVVLEDSIDDDEVTeendnTYRYLKDNGVEVRFD 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 487691887 108 GRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIeDAPQLAETYQREFNRL 164
Cdd:cd09131   88 SPSVTTHTKLVVIDGRTVYVGSHNWTYSALDYNHEASVLI-ESPEVADFAINYFDSI 143

Putative catalytic domain, repeat 1, of uncharacterized hypothetical proteins similar to Nuc, an endonuclease from Salmonella typhimurium; Putative catalytic domain, repeat 1, of uncharacterized hypothetical proteins, which show high sequence homology to the endonuclease from Salmonella typhimurium and vertebrate phospholipase D6. Nuc and PLD6 belong to the phospholipase D (PLD) superfamily. They contain a short conserved sequence motif, the HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which characterizes the PLD superfamily and is essential for catalysis. Nuc and PLD6 utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit. However, proteins in this subfamily have two HKD motifs in a single polypeptide chain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  35 RPALEIVLGAINNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTAVTY-LINQGVPVHLNGRY--- 110
Cdd:cd09172    8 REALLAFLDEARSAGSSIRLAIYELDDPEIIDALKAAKDRGVRVRIILDDSSVTGDPTEESAaATLSKGPGALVKRRhss 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 487691887 111 AIMHNKFMVIDGKN----VQTGSFNYTASAVSRNAENVLLIEDAPqLAETYQREFNRL 164
Cdd:cd09172   88 GLMHNKFLVVDRKDgpnrVLTGSTNFTTSGLYGQSNNVLIFRNPA-FAAAYLAYWNTL 144

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  33 DGRPALEIVLGAINNARQSIDVAAYSFTS----KPVATALAGANRRGVAVRVVADEKANSD-RYTAVTYLINQGVPVHL- 106
Cdd:COG1502   22 DGDEAFAALLEAIEAARRSIDLEYYIFDDdevgRRLADALIAAARRGVKVRVLLDGIGSRAlNRDFLRRLRAAGVEVRLf 101

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 487691887 107 -------NGRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAE------NVLLIEDaPQLAEtYQREFNRLWDEGT 169
Cdd:COG1502  102 npvrllfRRLNGRNHRKIVVIDGRVAFVGGANITDEYLGRDPGfgpwrdTHVRIEG-PAVAD-LQAVFAEDWNFAT 175

Putative catalytic domain, repeat 2, of uncharacterized phospholipase D-like proteins; Putative catalytic domain, repeat 2, of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze transphosphatidylation of phospholipids to acceptor alcohols. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  37 ALEIVLGAINNARQSIDVAAYSFTS-KPVATALAGANRRGVAVRVVADEKANSDRYTA--VTYLINQGVPVHLNGRYAI- 112
Cdd:cd09128   11 AREALLALIDSAEESLLIQNEEMGDdAPILDALVDAAKRGVDVRVLLPSAWSAEDERQarLRALEGAGVPVRLLKDKFLk 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 487691887 113 MHNKFMVIDGKNVQTGSFNYTASAVSRNAEnVLLIEDAPQLAETYQREFNRLW 165
Cdd:cd09128   91 IHAKGIVVDGKTALVGSENWSANSLDRNRE-VGLIFDDPEVAAYLQAVFESDW 142

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  45 INNARQSIDVAAYSFTS-KPVATALAGANRRGVAVRVVAD--EKANS-DRYTAVTYLINQGVPVHL--------NGRYAI 112
Cdd:cd09132    8 IEGAERSLLIVGYSAYKvSELLQALAAALERGVQVRVVVEssEKAGSvLSLDEDELMWPKLAGATLyvwpekkrPGKRAS 87

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 487691887 113 MHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLI 147
Cdd:cd09132   88 LHAKVIVADRRRLLVTSANLTGAGMERNIEAGVLV 122

Putative catalytic domain, repeat 1, of vertebrate phospholipases, PLD3, PLD4 and PLD5, viral envelope proteins K4 and p37, and similar proteins; Putative catalytic domain, repeat 1, of vertebrate phospholipases D, PLD3, PLD4, and PLD5 (EC 3.1.4.4), viral envelope proteins (vaccinia virus proteins K4 and p37), and similar proteins. Most family members contain two copies of the HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue), and have been classified into the phospholipase D (PLD) superfamily. Proteins in this subfamily are associated with Golgi membranes, altering their lipid content by the conversion of phospholipids into phosphatidic acid, which is thought to be involved in the regulation of lipid movement. ADP ribosylation factor (ARF), a small guanosine triphosphate binding protein, might be required activity. The vaccinia virus p37 protein, encoded by the F13L gene, is also associated with Golgi membranes and is required for the envelopment and spread of the extracellular enveloped virus (EEV). The vaccinia virus protein K4, encoded by the HindIII K4L gene, remains to be characterized. Sequence analysis indicates that the vaccinia virus proteins K4 and p37 might have evolved from one or more captured eukaryotic genes involved in cellular lipid metabolism. Up to date, no catalytic activity of PLD3 has been shown. Furthermore, due to the lack of functional important histidine and lysine residues in the HKD motif, mammalian PLD5 has been characterized as an inactive PLD. The poxvirus p37 proteins may also lack PLD enzymatic activity, since they contain only one partially conserved HKD motif (N-x-K-x(4)-D).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  45 INNARQSIDVAAY--SFTSKPVAT------------ALAGANRRGVAVRVVADEKANSDRYTAVTYLINQG------VPV 104
Cdd:cd09106   28 ISSAKKSIDIASFywNLRGTDTNPdssaqegedifnALLEAAKRGVKIRILQDKPSKDKPDEDDLELAALGgaevrsLDF 107

                         90       100
                 ....*....|....*....|....*..
gi 487691887 105 HLNGRYAIMHNKFMVIDGKNVQTGSFN 131
Cdd:cd09106  108 TKLIGGGVLHTKFWIVDGKHFYLGSAN 134

Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  42 LGAINNARQSIDVAAYSFTSKPVAT----ALAGANRRGVAVRVVADekANSDRYT---AVTYLINQGVPV---------- 104
Cdd:cd09157   11 LEAIDAARHSIALSSYIFDNDGVGRefvdALAEAVARGVDVRVLID--GVGARYSrpsIRRRLRRAGVPVarflpprlpp 88

                         90       100       110
                 ....*....|....*....|....*....|
gi 487691887 105 ---HLNGRyaiMHNKFMVIDGKNVQTGSFN 131
Cdd:cd09157   89 rlpFINLR---NHRKILVVDGRTGFTGGMN 115

Catalytic domain, repeat 1, of Escherichia coli cardiolipin synthase and similar proteins; Catalytic domain, repeat 1, of Escherichia coli cardiolipin (CL) synthase and similar proteins. Escherichia coli CL synthase (EcCLS), specified by the cls gene, is the prototype of this family. EcCLS is a multi-pass membrane protein that catalyzes reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of EcCLS consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. EcCLS can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, EcCLS utilizes a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  32 SDGRPALEIVLGAINNARQSIDVAAYSF----TSKPVATALAGANRRGVAVRVVADEKANSD--RYTAVTYLINQGVPVH 105
Cdd:cd09152    8 TDYDAVIDRLIADIDAAKHHVHLLFYIWaddgTGDRVAEALERAAKRGVTCRLLLDAVGSRAffRSSLWKRLREAGVEVV 87

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 487691887 106 --LNGRYAIM---------HNKFMVIDGKNVQTGSFN 131
Cdd:cd09152   88 eaLPLRLFRRrlarfdlrnHRKIAVIDGRIAYTGSQN 124

Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  34 GRPALEIVLGAINNARQSI-DVAAYSFTSKPVATALAGANRRGVAVRVVADEKAN---SD--RYTAVTYLINQGVPVHLN 107
Cdd:cd09162    9 GDPLYEALLSAIFEAEHRIwIVTPYFVPDEVLLRALRLAARRGVDVRLIVPKRSNhriADlaRGSYLRDLQEAGAEIYLY 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 487691887 108 GRyAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDAPQLAE 155
Cdd:cd09162   89 QP-GMLHAKAVVVDDKLALVGSANLDMRSLFLNYEVAVFFYSPADIKE 135

N-terminal phospholipase D-like domain of the protein, Family with sequence similarity 83D; N-terminal phospholipase D (PLD)-like domain of the protein Family with sequence similarity 83D (FAM83D), also known as spindle protein CHICA. CHICA is a cell-cycle-regulated spindle component, which localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. CHICA is required to localize the chromokinesin Kid to the mitotic spindle and serves as a novel interaction partner of Kid, which is required for the generation of polar ejection forces and chromosome congression. Since the N-terminal PLD-like domain of FAM83D shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, FAM83D may share a similar three-dimensional fold with PLD enzymes, but is unlikely to carry PLD activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  16 PAFATAA----PVLTAGFSPSDGRPAL---EIVLGAINNARQSIDVAAYSFTSKPVATALAGA-NRRGVAVRVVADEKAN 87
Cdd:cd09184   97 PAFTTGSyrgvTRVEAHFQPSYGDCIYgckEAARRQIRSAREVIALVMDSFTDLDIFRDLREAcRKRRVPVYILLDQSSV 176

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  88 SD---------------------RYTAVTYLINQGVPVhlNGRyaiMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLL 146
Cdd:cd09184  177 SHflqmcknlgvhleqeklmrvrTITGNTYYTRSGAKI--IGK---VHEKFMLIDGIKVATGSYSFTWTDGKLNSSNLLI 251

                        170
                 ....*....|....*....
gi 487691887 147 IedAPQLAETYQREFNRLW 165
Cdd:cd09184  252 L--SGQVVEKFDLEFRILY 268

Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 487691887  32 SDGRPALEIVLGAINNARQSIDVAAYSF----TSKPVATALAGANRRGVAVRVVAD 83
Cdd:cd09156    1 ADGVEAYQALIQLIESAKHSIDVCTFILgddaTGRRVIDALARKAREGVEVRLLLD 56

Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  32 SDGRPALEIVLGAINNARQSIDVAAYSFTSKPVATALAG----ANRRGVAVRVVADeKANSDRYTAVTYLINQ------- 100
Cdd:cd09111    2 EDGLDALAARLALIRSAERSIDLQYYIWHDDESGRLLLGelleAADRGVRVRLLLD-DLGTSGRDRLLAALDAhpnievr 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 487691887 101 ----------------GVPVHLNGRyaiMHNKFMVIDGK 123
Cdd:cd09111   81 lfnpfrnrggrlleflTDFSRLNRR---MHNKLFIVDGA 116

Middle phospholipase D-like domain of the transcriptional regulator TrmB and similar proteins; Middle phospholipase D (PLD)-like domain of the transcriptional regulator TrmB and similar proteins. TrmB acts as a bifunctional sugar-sensing transcriptional regulator which controls two operons encoding maltose/trehalose and maltodextrin ABC transporters of Pyrococcus fruiosus. It functions as a dimer. Full length TrmB includes an N-terminal DNA-binding domain, a C-terminal sugar-binding domain and middle region that has been named as a PLD-like domain. The middle domain displays homology to PLD enzymes, which contain one or two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) per chain. The HKD motif characterizes the PLD superfamily. Due to the lack of key residues related to PLD activity in the PLD-like domain, members of this subfamily are unlikely to carry PLD activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  45 INNARQSIDVAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYtavtYLINQGVPVHLNGRYAIMhnkfMVIDGKN 124
Cdd:cd09124   19 INSAKEEIYISLPSEELEELLEELEKAAERGVKVVIIIFGDDDLDDL----DSPAIEVRVREGGGRPFL----LIVDSKE 90

                         90       100
                 ....*....|....*....|....*....
gi 487691887 125 VQTGSFNYTASAV---SRNAENVLLIEDA 150
Cdd:cd09124   91 ALIGPSSEEEETYalyTENPALVLLAREY 119

N-terminal phospholipase D-like domain of proteins from the Family with sequence similarity 83; N-terminal phospholipase D (PLD)-like domain of vetebrate proteins from the Family with sequence similarity 83 (FAM83), which is comprised of 8 members, designated FAM83A through FAM83H. Since the N-terminal PLD-like domain of FAM83 proteins shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, the FAM83 proteins may share a similar three-dimensional fold with PLD enzymes, but are unlikely to carry PLD activity. Members of the FAM83 are mostly uncharacterized proteins. FAM83A, also known as tumor antigen BJ-TSA-9, is a novel tumor-specific gene highly expressed in human lung adenocarcinoma. FAM83D, also known as spindle protein CHICA, is a cell-cycle-regulated spindle component which localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. The gene encoding protein FAM83H is the first gene involved in the etiology of amelogenesis imperfecta (AI), that encodes a non-secreted protein due to the absence of a signal peptide. Defects in gene FAM83H cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI). FAM83B, FAM83C, FAM83F, and FAM83G are uncharacterized proteins present across vertebrates while FAM83E is an uncharacterized protein found only in mammals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  31 PSDGRPAL-EIVLGAINNARQSIDVAAYSFTSKPV-ATALAGANRRGVAVRVVADE-------------KANSDRY---- 91
Cdd:cd09119  116 PKEGAPNIkDLVRRMIQQAQKVIAVVMDVFTDVDIfCDLLEAANKRGVAVYILLDQgnvkhflemcdklQLSDEHLknmr 195

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 487691887  92 ----TAVTYLINQGVPVHlnGRyaiMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDapQLAETYQREFNRLW 165
Cdd:cd09119  196 vrsvGGKTYCSRSGKKFK--GQ---MKEKFLLVDGDRVVSGSYSFTWSDAKLHRSMLSVLTG--QVVESFDEEFRILY 266

Phospholipase D. Active site motifs; Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, aspartic acid, and/or asparagine residues which may contribute to the active site. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

                           10        20
                   ....*....|....*....|..
gi 487691887   112 IMHNKFMVIDGKNVQTGSFNYT 133
Cdd:smart00155   4 VLHTKLMIVDDEIAYIGSANLD 25

Putative catalytic domain, repeat 2, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 2, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  45 INNARQSID-VAAYSFTSKPVATALAGANRRGVAVRVVADEKANSDRYTA----VTY---LINQGV-------------- 102
Cdd:cd09113   26 LKNAKREVLiVSPYFVPGDEGVALLAELARRGVRVRILTNSLAATDVPAVhsgyARYrkrLLKAGVelyelkpdaakrkr 105

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 487691887 103 -PVHLNGRYAIMHNKFMVIDGKNVQTGSFNYTASAVSRNAENVLLIEDaPQLAETYQREFNR 163
Cdd:cd09113  106 lRGLFGSSRASLHAKSFVIDDRLVFVGSFNLDPRSAYLNTEMGLVIDS-PELAAQLRAAMEE 166

palmytilated EEV membrane glycoprotein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  38 LEIVLGAINNARQSIDVAAYSFTskPVATA--------------LAGANRRGVAVRVVADEKANSDRYT--AVTYLINQG 101
Cdd:PHA03003 218 ADVVLHKIKSAKKSIDLELLSLV--PVIREddkttywpdiynalIRAAINRGVKVRLLVGSWKKNDVYSmaSVKSLQALC 295

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 487691887 102 VPVHLNGR-YAIMHN-KFMVIDGKNVQTGSFNYTAS------AVSRNAENvlliedaPQLAETYQREFNRLW 165
Cdd:PHA03003 296 VGNDLSVKvFRIPNNtKLLIVDDEFAHITSANFDGThylhhaFVSFNTID-------KELVKELSAIFERDW 360

N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain; N-terminal putative catalytic domain of uncharacterized prokaryotic and archeal HKD family nucleases fused to a DEAD/DEAH box helicase domain. All members of this subfamily are uncharacterized. Other characterized members of the superfamily that have a related domain architecture ( containing a DEAD/DEAH box helicase domain), include the DNA/RNA helicase superfamily II (SF2) and Res-subunit of type III restriction endonucleases. In addition to the helicase-like region, members of this subfamily also contain one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in the N-terminal putative catalytic domain. The HKD motif characterizes the phospholipase D (PLD, EC 3.1.4.4) superfamily.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 487691887 113 MHNKFMVIDGKNVQT---GSFNYTASAVSRNAE-NVLLI--EDApQLAETYQREFNRLW 165
Cdd:cd09204   82 FHAKGYIFEHEDYYTiivGSSNLTQSALKSNYEwNLKVSstENG-DLVEQVLEEFERLW 139

cardiolipin synthase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487691887  21 AAPVLTAGfsPSDGRPALE-IVLGAINNARQSIDVAA-YSFTSKPVATALAGANRRGVAVRVVADEKANS--DRYTAVTY 96
Cdd:PRK12452 330 AVQIVASG--PSSDDKSIRnTLLAVMGSAKKSIWIATpYFIPDQETLTLLRLSAISGIDVRILYPGKSDSiiSDQASQSY 407